Cobalt-catalyzed ortho-alkenylation of aromatic aldimines via chelation-assisted C-H bond activation

Article abstract of DOI:10.1016/j.tet.2013.02.092

An ortho-alkenylation reaction of an aromatic aldimine with an internal alkyne is efficiently promoted by a cobalt catalyst generated from CoBr ₂, triarylphosphine, and ⁱPrMgBr. The reaction takes place under mild room-temperature co

Full text of DOI:10.1016/j.tet.2013.02.092

Tetrahedron xxx (2013) 1e7
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Cobalt-catalyzed ortho-alkenylation of aromatic aldimines via
chelation-assisted CeH bond activation
*
Takeshi Yamakawa, Naohiko Yoshikai
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link,
Singapore 637371, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
An ortho-alkenylation reaction of an aromatic aldimine with an internal alkyne is efficiently promoted by
a cobalt catalyst generated from CoBr2, triarylphosphine, and PrMgBr. The reaction takes place under
mild room-temperature conditions to afford, upon acidic hydrolysis, a variety of ortho-alkenylated aro-
matic aldehydes in moderate to excellent yields. The neighboring formyl and alkenyl groups in the
product can be utilized as synthetic handles for the facile construction of indene and naphthalene
carbocycles.
i
Received 30 November 2012
Received in revised form 16 February 2013
Accepted 26 February 2013
Available online xxx
Keywords:
Ó 2013 Elsevier Ltd. All rights reserved.
Cobalt catalysis
CeH bond functionalization
Aldimine
Alkyne
Carbocycles
1. Introduction
involves intramolecular nucleophilic attack of an alkenylrhenium
intermediate to the C]N bond as the key cyclization step.4,5 Fagnou
Since the groundbreaking work of Murai and coworkers on the
ruthenium-catalyzed ortho-alkylation reaction of aromatic ketones
with olefins,1 chelation-assisted CeH bond activation has been
extensively practiced as a powerful strategy for the regioselective
functionalization of arenes.2 Besides the precise regiocontrol of CeH
functionalization, this strategy is particularly attractive for the con-
struction of carbo- and heterocycles through intramolecular reaction
between the directing group and the newly introduced functional
group (Scheme 1a). This can be achieved by two complementary
approaches, that is, (1) simple CeH bond functionalization followed
by appropriate functional group interconversion and intramolecular
cyclization and (2) direct annulation through sequential CeH bond
functionalization/intramolecular cyclization. While the latter direct
approach allows straightforward construction of a single type of
carbo- or heterocycle in one shot, the former stepwise approach
enables, depending on the versatility of the directing group, con-
struction of a diverse set of cyclic structures in a flexible manner.3
In theabove context, aromatic aldimines and alkynes have proven
to be useful starting materials for the construction of carbo- and
heterocycles based on the direct annulation approach. Kuninobu,
Takai and coworkers developed a rhenium-catalyzed annulation
reaction for the synthesis of indene derivatives, which supposedly
and coworkers developed a rhodium-catalyzed oxidative annulation
reaction leading to isoquinolines through CeN reductive elimination
of an alkenylrhodium(III) intermediate.6e8 On the other hand, aldi-
mine has rarely been used as a directing group for simple ortho-
alkenylation reaction with alkynes, regardless of the versatility of
aldimine and its hydrolyzed form (i.e., aldehyde).9,10 Recently, we
reported on
a cobalt-catalyzed ortho-alkenylation reaction of
aromatic ketimines with alkynes under mild room-temperature
conditions.11 Upon extension of the scope of the cobalt cata-
lysis,12e14 we have successfully developed a new cobalt-based cata-
lytic system that allows efficient ortho-alkenylation of aromatic
aldimines with internal alkynes, which is reported herein. The
resulting ortho-alkenylated aromatic aldehyde serves as a useful
platformfor theconstructionofindene andnaphthalene carbocycles.
2. Results and discussion
Our initial study focused on the screening of reaction conditions
for the alkenylation of o-tolualdehyde-derived aldimine 1a with
diphenylacetylene 2a (Table 1). The catalytic system consisting of
t
CoBr2 (5 mol %), P(3-ClC6H4)3 (10 mol %), BuCH2MgBr (50 mol %),
and pyridine (80 mol %), which we previously used for the ortho-
alkenylation of aromatic ketimines,11 promoted the reaction at room
temperature (25 ꢀC) to only a moderate extent, affording the adduct
3aa in 29% GC yield (entry 1). Pyridine was not a critical additive, as
the product yield increased to 39% in its absence (entry 2). A serious
* Corresponding author. Tel.: þ65 6592 7768; fax: þ65 6791 1961; e-mail ad-
dress: nyoshikai@ntu.edu.sg (N. Yoshikai).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.02.092
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T. Yamakawa, N. Yoshikai / Tetrahedron xxx (2013) 1e7
(a)
mass balance achieved with P(4-MeOC6H4)3 (entry 3). While it did
not particularly improve the product yield (26%), 1a was recovered
in a much better yield of 68%. We also noted that the product 3aa
consisted of a mixture of E/Z isomers (62/38) by 1H NMR analysis.
Increasing the reaction temperature to 60 ꢀC slightly improved the
product yield to 44% maintaining a reasonable mass balance (48%
recovery), while the Z isomer became the major isomer (E/Z¼41/59).
Next, we screened a series of Grignard reagents including PhMgBr,
MeMgCl, nBuMgBr, and iPrMgBr to observe their significant in-
fluences on the catalytic activity (entries 5e8). Among them, iPrMgBr
gave rise to the highest catalytic activity,14 resulting in the formation
of 3aa in 88% yield with an E/Z ratio of 18:82 (entry 8). However, the
L
L'
L
cat. [M]
C–H
FGI +
cyclization
H
R
R'
carbo/heterocycles
functionalization
cat. [M]
annulation via C–H functionalization
(b) Kunibobu/Takai (ref 4)
t
t
N Bu
R1
N Bu
Re
R1
t
NH Bu
cat. ReI
H
i
reaction with PrMgBr (as well as MeMgBr and nBuMgBr) was ac-
+
R1
companied by a nonnegligible amount of amine 4 arising from
Grignard addition to the C]N bond. This side reaction could be
suppressed by lowering the temperature to 25 ꢀC and increasing the
loading of P(4-MeOC6H4)3e20 mol %, with a slight decrease in the
product yield (entry 9). With additional fine-tuning of the reaction
conditions, we eventually identified the combination of CoBr2
(5 mol %), P(3-MeC6H4)3 (20 mol %), and iPrMgBr (50 mol %) as the
optimum catalytic system, affording 3aa in 87% yield with an E/Z ratio
ofca. 4:1(entry10). Efforts toimprovetheE/Zratiowereunsuccessful.
With the optimized catalytic system in hand, we explored the
scope of the ortho-alkenylation reaction (Scheme 2). A variety of
H
R2
R2
R2
(c) Fagnou (ref 6)
t
t
Bu
N Bu
R1
R2
cat. RhIII
[O]
N
N
RhIII
R1
+
R1
H
R2
R2
(c) This work
R3
R1
CoBr2 (5 mol%)
NPMP
R1
R2
CHO
R2
R1
cat. Co H+
R2
P(3-MeC6H4)3 (20 mol%)
R2
R4
NPMP
R1
CHO
R3
H+
+
iPrMgBr (50 mol%)
R1
+
H
THF, rt, 12 h
R2
R3
R1
R3
1
5
2
(1.5 equiv)
R2
O
N
R
Scheme 1. Construction of carbo- and heterocycles via chelation-assisted CeH bond
functionalization.
OMe
R
CHO
CHO
Ph
CHO
Ph
Table 1
Ph
Screening of reaction conditionsa
Ph
Ph
Ph
CoBr2 (5 mol%)
5ba (R = Ph), 88%
5ca (R = OMe), 90%
5da (R = CF3), 68%
Me NPMP
PAr3 (10 mol%)
Ph
5fa (R = OMe), 76%
5ga (R = Br), 59%
Me NPMP
Me NHPMP
R
RMgX (50 mol%)
5ea, 66%
+
+
THF, temp, time
Ph
OMe
Ph
Ph
3aa
MeO
MeO
CHO
CHO
F3C
CHO
1a
4
2a
(1.5 equiv)
Ph
Ph
Ph
Entry
PAr3
RMgX
Temp (ꢀC)
Yield (%)b
Ph
Ph
Ph
3aa (E/Z)
4
5ja, 53%
5ha, 78%
5ia, 94%
83% [10 mmol scale]
a
1c
2
3
4
5
P(3-ClC6H4)3
P(3-ClC6H4)3
tBuCH2MgBr
tBuCH2MgBr
tBuCH2MgBr
tBuCH2MgBr
PhMgBr
25
25
25
60
60
60
60
60
25
25
29 (N.D.)d
39 (N.D.)d
26 (62/38)
44 (41/59)
55 (25/75)
60 (17/83)
68 (22/78)
88 (18/82)
76 (79/21)
87 (79/21)
0
0
0
0
0
6
32
12
2
(E/Z = 79:21)
Me NPMP
Me NPMP
CHO
P(4-MeOC6H4)3
P(4-MeOC6H4)3
P(4-MeOC6H4)3
P(4-MeOC6H4)3
P(4-MeOC6H4)3
P(4-MeOC6H4)3
P(4-MeOC6H4)3
P(3-MeC6H4)3
Ph
6
7
8
MeMgCl
N
nPr
nPr
iPr
Ph
nBuMgBr
Me
Me
iPrMgBr
3ab, 94%b
3ac, 92%b,c
(r.r. = 96:4)
5ka, 82%
9e
10e
iPrMgBr
(E/Z = 63:37)
iPrMgBr
4
F
NPMP
a
CHO
Reaction was performed on a 0.3 mmol scale.
b
c
Determined by GC (entries 1 and 2) or 1H NMR (entries 3e10).
Pyridine (80 mol %) was added.
SiMe3
d
e
Ph
N
Me
N.D.¼not determined.
Me
F
Me
20 mol % of ligand was used.
3ld, 97%b
5ke, 86%
(E/Z = 86:14)
problem we observed in these reactions was a poor mass balance.
Thus, for entries 1 and 2, the aldimine 1a was recovered only in 13%
and 6% yields, respectively, for unknown reasons. Throughout
screening of other triarylphosphine ligands, we observed a better
Scheme 2. Scope of cobalt-catalyzed ortho-alkenylation of aromatic aldimines. The
reaction was performed on a 0.3 mmol scale unless otherwise noted. aThe reaction was
performed on a 10 mmol scale for 24 h. bThe products were obtained without acidic
hydrolysis. cr.r.¼regioisomer ratio. The major regioisomer is shown.
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T. Yamakawa, N. Yoshikai / Tetrahedron xxx (2013) 1e7
3
ortho-monosubstituted aromatic aldimines smoothly participated
in the reaction with diphenylacetylene to afford, upon acidic hy-
drolysis, the corresponding ortho-alkenylated aromatic aldehydes
5bae5ia in moderate to good yields. It is notable that, unlike the
model substrate 1a, these aldimine substrates afforded cis-alke-
nylation products (i.e., E isomers) with exclusive stereoselectivity.
The reaction tolerated both electron-donating (i.e., methoxy, mor-
pholino) and electron-withdrawing (i.e., trifluoromethyl) groups. A
bromide substituent on the aldimine substrate remained un-
touched under the reaction conditions (see compound 5ga), which
would be useful for further synthetic transformations. The reaction
of 1-naphthyl aldimine could be performed on a 10 mmol scale to
afford the alkenylation product 5ia in multigram quantities without
significant decrease in the reaction efficiency. The presence of
a meta-trifluoromethyl group directed the reaction to take place
exclusively at the sterically less hindered position to afford the
adduct 5ja in 53% yield with an E/Z ratio of ca. 4:1. The C2 position
of indole was also alkenylated with diphenylacetylene in 82% yield
with extensive E/Z isomerization (see the product 5ka).
It was rather curious to find that parent benzaldimine was nearly
unreactive toward diphenylacetylene under the present conditions,
where formation of only a trace amount of a monoalkenylation
product was indicated by GCeMS analysis. At this moment, we do
not have a rationale for this observation. It should also be noted that
the PMP group was a much better N-substituent than others. Thus,
the reaction of 1-naphthaldimine derivatives bearing N-phenyl and
N-tert-butyl groups with diphenylacetylene afforded the alkeny-
lated aldehyde 5ia in 58% and 2% yields, respectively.
5ia afforded indenol 6 in 74% yield. Alternatively, 5ia was first
subjected to the addition of phenyllithium followed by BF3-medi-
ated cyclization, affording indene 7 in 97% overall yield. Facile
conversion of the formyl group to an ethynyl group using lithiated
trimethylsilyldiazomethane provides further opportunities for
carbocyclization. Thus, the enyne 8 readily participated in PtCl2-
catalyzed carbocyclization to afford a phenanthrene derivative 9 in
82% yield.16 Furthermore, Sonogashira coupling of 8 with 4-
iodoanisole was followed by N-iodosuccinimide-mediated iodo-
carbocyclization to afford a polyarylated iodophenanthrene 10 in
63% overall yield.17
3. Conclusion
In summary, we have developed an ortho-alkenylation reaction
of aromatic aldimines with internal alkynes promoted by a cobalt
i
catalyst generated from CoBr2, triarylphosphine, and PrMgBr. The
reaction affords a variety of ortho-alkenylated aromatic aldehydes
in moderate to excellent yields under mild room-temperature
conditions. The reaction generally takes place with cis-stereo-
selectivity, while significant E/Z isomerization is observed in some
cases for currently unknown reasons. The formyl and alkenyl
groups in the product allow convenient preparation of indene and
naphthalene carbocycles, and should also hold promise for further
structural diversification. Further studies on the mechanism, de-
velopment, and application of CeH alkenylation reactions are cur-
rently in progress in our laboratory.
The present reaction was applicable to other alkynes such
as 5-decyne, 4-methylpent-2-yne, 1-phenyl-1-propyne, and
1-trimethylsilyl-1-propyne, which afforded the adducts 3ab, 3ac,
3ld, and 5ke, respectively, in good yields. The reaction of the latter
three alkynes took place with exclusive regioselectivity, where the
new CeC bond was formed on the less hindered acetylenic carbon
atom.11,13b,15 Note that the products 3ab, 3ac, and 3ld as well as 3aa
in Table 1 were isolated in the form of aldimine without hydrolysis,
as the acidic treatment of the crude reaction mixture caused not
only the desired hydrolysis but also intramolecular cyclization of
the aldimine and the alkenyl moieties, resulting in a mixture of an
alkenylated aldehyde and an aminoindene derivative.11a
As discussed in the Introduction, the ortho formyl/alkenyl
groups in the present alkenylation product serve as versatile syn-
thetic handles for the construction of carbocycles. As a demon-
stration of this idea, the adduct 5ia was diversified into indene and
naphthalene derivatives (Scheme 3). BF3-mediated cyclization of
4. Experimental section
4.1. General
All reactions dealing with air- and moisture-sensitive com-
pounds were performed by standard Schlenk techniques in oven-
dried reaction vessels under nitrogen atmosphere. Analytical
thin-layer chromatography (TLC) was performed on Merck 60 F254
silica gel plates. Flash chromatography was performed using
40e63 mm silica gel (Si 60, Merck). 1H and 13C nuclear magnetic
resonance (NMR) spectra were recorded on a JEOL ECA-400
(400 MHz) spectrometer, and are reported in parts per million
(ppm) downfield from an internal standard, tetramethylsilane
(0 ppm) and CHCl3 (77 ppm), respectively. Gas chromatographic
(GC) analysis was performed on a Shimadzu GC-2010 system
equipped with an FID detector and a capillary column, DB-5 (Agi-
lent J&W, 0.25 mm i.d.ꢁ30 m, 0.25
mm film thickness). High-
resolution mass spectra (HRMS) were recorded with a Q-Tof Pre-
mier LC HR mass spectrometer. Unless otherwise noted, commer-
cial reagents were purchased from Aldrich, Alfa Aesar, and other
commercial suppliers and were used as received. Cobalt(II) bro-
mide (99%) were purchased from Aldrich. THF was distilled over
Na/benzophenone before use.
OH
Ph
Ph
Ph
CHO
a
b, c
Ph
Ph
74%
97%
Ph
Ph
6
5ia
7
4.2. General procedure for preparation of aromatic aldimine
75%
d
To a solution of aromatic aldehyde (50 mmol) in EtOH (100 mL)
was added p-anisidine (60 mmol) at room temperature. After
stirring for 12 h, the reaction mixture was concentrated under
reduced pressure. The crude product was purified by re-
crystallization or silica gel chromatography. Spectral data of 1a,18
1b,19 1h,20 1i,21 and 1k22 showed good agreement with the liter-
ature data.
I
Ar
e
f, g
82%
63%
Ph
Ph
Ph
Ph
Ph
Ph
9
8
10
(Ar = 4-MeOC6H4)
Scheme 3. Transformation of ortho-alkenylation product. Reaction conditions:
a) BF3$OEt2 (2 equiv), CH2Cl2, 0 ꢀC; b) PhLi (1.5 equiv), THF, ꢂ78 ꢀC; c) BF3$OEt2
(2 equiv), CH2Cl2, rt; d) Me3SiCHN2 (1.2 equiv), BuLi (1.2 equiv), THF, ꢂ78 ꢀC to rt;
e) PtCl2 (10 mol %), toluene, 90 ꢀC; f) PdCl2(PPh3)2 (2 mol %), CuI (1 mol %), 4-MeOC6H4I
(2 equiv), NEt3, 55 ꢀC; g) NIS (3 equiv), CH2Cl2, 50 ꢀC.
4.2.1. (E)-4-Methoxy-N-(2-methoxybenzylidene)aniline
(1c). Purified by recrystallization from hexane/CH2Cl2. Yellow solid
(58%); Mp¼43e44 ꢀC; 1H NMR (400 MHz, CDCl3):
d 3.83 (s, 3H),
3.90 (s, 3H), 6.91e6.96 (m, 3H), 7.03 (t, J¼7.8 Hz, 1H), 7.24 (app. d,
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4
T. Yamakawa, N. Yoshikai / Tetrahedron xxx (2013) 1e7
1
J¼9.1 Hz, 2H), 7.42 (td, J¼8.0 Hz, 1.8 Hz, 1H), 8.14 (dd, J¼7.8, 1.8 Hz,
1H), 8.94 (s,1H); 13C NMR (100 MHz, CDCl3):
55.6, 55.7,111.2,114.4
159.09 (d, JCeF¼244.3 Hz); HRMS (ESIþ) Calcd for C14H12NOF2
[MþH]þ 248.0887, found 248.0888.
d
(2C), 121.0, 122.5 (2C), 125.1, 127.5, 132.5, 145.8, 154.6, 158.2, 159.5;
HRMS (ESIþ) Calcd for
C
15H16NO2 [MþH]þ 242.1181, found
4.3. General procedure for cobalt-catalyzed ortho-alkenyla-
tion of aromatic aldimines
242.1184.
4.2.2. (E)-4-Methoxy-N-(2-(trifluoromethyl)benzylidene)aniline
(1d). Purified by silica gel chromatography (eluent: hexane/
EtOAc/NEt3¼20:1:1). Yellow solid (96%); Mp¼55e56 ꢀC; 1H
In a Schlenk tube equipped with a stirrer bar were placed
aldimine (0.3 mmol), P(3-MeC6H4)3 (18.3 mg, 0.06 mmol, 20 mol %),
CoBr2 (0.075 M solution in THF, 0.2 mL, 0.015 mmol, 5 mol %), and
THF (0.21 mL). To the mixture was added a THF solution of iPrMgBr
(1.03 M, 0.14 mL, 0.15 mmol) dropwise at 0 ꢀC. After stirring for
30 min, diphenylacetylene (0.23 M solution in THF, 0.2 mL,
0.45 mmol) was added. The resulting mixture was allowed to room
temperature and stirred for 12 h, followed by dilution with THF
(1 mL) and quenching with water (0.5 mL) and 1 N HCl (0.5 mL). The
resulting mixture was stirred for 1 h and then extracted with EtOAc
(4 mLꢁ3). The combined organic layer was dried over Na2SO4 and
concentrated under reduced pressure. The crude product was pu-
rified by silica gel chromatography to afford the desired ortho-
alkenylated aryl aldehyde. Characterization data for the compound
5ka have been reported in the literature.9b
NMR (400 MHz, CDCl3):
d
3.84 (s, 3H), 6.96 (app. d, J¼8.7 Hz,
2H), 7.27 (app. d, J¼8.7 Hz, 2H), 7.54 (t, J¼8.2 Hz, 1H), 7.65
(t, J¼7.3 Hz, 1H), 7.73 (d, J¼8.2 Hz, 1H), 8.44 (d, J¼7.8 Hz,
1H), 8.84e8.85 (m, 1H); 13C NMR (100 MHz, CDCl3):
d 55.7,
1
114.7 (2C), 122.7 (2C), 124.5 (q, JCeF¼277.8 Hz), 125.9
3
2
(q, JCeF¼5.7 Hz), 128.4, 129.6 (q, JCeF¼31.6 Hz), 130.5, 132.2,
134.6, 144.6, 154.2, 159.0; HRMS (ESIþ) Calcd for C15H13NOF3
[MþH]þ 280.0949, found 280.0950.
4.2.3. (E)-4-Methoxy-N-(2-morpholinobenzylidene)aniline
(1e). Purified by recrystallization from hexane/CH2Cl2. Yellow solid
(80%); 1H NMR (400 MHz, CDCl3):
d 3.02e3.04 (m, 4H), 3.85 (s, 3H),
3.86e3.89 (m, 4H), 6.95 (app. d, J¼9.2 Hz, 2H), 7.12 (dd, J¼8.2,
0.9 Hz, 1H), 7.17 (t, J¼7.3 Hz, 1H), 7.23 (app. d, J¼11.9 Hz, 2H),
7.41e7.46 (m, 1H), 8.09 (dd, J¼7.8, 1.6 Hz, 1H), 8.87 (s, 1H); 13C NMR
4.3.1. (E)-N-(2-((E)-1,2-Diphenylvinyl)benzylidene)-4-
methoxyaniline (3aa). The reaction mixture was not treated with
aq HCl (i.e., imine was not hydrolyzed). Purified by silica gel chro-
matography (eluent: hexane/EtOAc/NEt3¼100:1:2). Red oil (78%)
consisting of a 79:21 mixture of alkene E/Z isomers as determined
by 1H NMR analysis; Rf 0.41 (hexane/EtOAc¼10:1); 1H NMR
(100 MHz, CDCl3):
d 53.7, 55.5, 67.1, 114.4, 118.8, 122.2, 123.7, 128.3,
129.8, 131.7, 145.4, 153.3, 156.3, 158.2; HRMS (ESIþ) Calcd for
C
18H21N2O2 [MþH]þ 297.1603, found 297.1602.
4.2.4. (E)-N-(2,5-Dimethoxybenzylidene)-4-methoxyaniline
(400 MHz, CDCl3, E-isomer): d 2.71 (s, 3H), 3.75 (s, 3H), 6.72e6.77
(1f). Purified by recrystallization from hexane/EtOAc/CHCl3. Yellow
(m, 4H), 6.99 (d, J¼6.4 Hz, 2H), 7.05e713 (m, 5H), 7.22e7.34 (m, 7H),
solid (78%); Mp¼76e77 ꢀC; 1H NMR (400 MHz, CDCl3):
d
3.83
8.50 (s, 1H); 13C NMR (100 MHz, CDCl3, E-isomer):
d
22.3, 55.6,114.2
(s, 3H), 3.86 (s, 3H), 3.86 (s, 3H), 6.88e7.01 (m, 5H), 7.24 (s, 3H), 7.68
(2C), 121.9 (2C), 127.1 (2C), 127.3, 127.7, 128.3 (2C), 128.6 (2C), 128.9,
129.4, 129.5 (2C), 130.1, 131.4, 133.6, 137.1, 139.4, 140.9, 142.3, 143.1,
146.1, 158.0, 159.6; HRMS (ESIþ) Calcd for C29H26NO [MþH]þ
404.2014, found 404.2014.
(d, J¼3.2 Hz, 1H), 8.90 (s, 1H); 13C NMR (100 MHz, CDCl3):
d 55.6,
56.0, 56.4, 110.4, 113.0, 114.5 (2C), 119.6, 122.6 (2C), 125.6, 145.7,
154.0, 154.2, 154.5, 158.3; HRMS (ESIþ) Calcd for C16H18NO3
[MþH]þ 272.1287, found 272.1284.
4.3.2. 3-(1,2-Diphenylvinyl)-[1,10-biphenyl]-2-carbaldehyde
(5ba). Purified by silica gel chromatography (eluent: hexane/
EtOAc¼25:1). Red oil (88%); Rf 0.21 (hexane/EtOAc¼10:1); 1H NMR
4.2.5. (E)-N-(5-Bromo-2-methoxybenzylidene)-4-methoxyaniline
(1g). Purified by recrystallization from hexane/EtOAc/CHCl3. Yel-
low solid (59%); Mp¼100e101 ꢀC; 1H NMR (400 MHz, CDCl3):
d
3.84
(400 MHz, CDCl3): d 6.95e6.97 (m, 2H), 7.07e7.15 (m, 4H),
(s, 3H), 3.89 (s, 3H), 6.83 (d, J¼8.7 Hz, 1H), 6.93 (app. d, J¼9.2, 2H),
7.22e7.43 (m, 12H), 7.56 (t, J¼7.8 Hz, 1H), 9.78 (s, 1H); 13C NMR
7.24e7.26 (m, 2H), 7.50 (dd, J¼9.2, 2.7 Hz,1H), 8.26 (d, J¼2.7 Hz,1H),
(100 MHz, CDCl3):
d 127.1 (3C), 127.6, 128.0, 128.2, 128.39 (2C),
8.84 (s, 1H); 13C NMR (100 MHz, CDCl3):
d
55.7, 56.0, 113.1, 113.8,
128.42 (2C), 128.8 (2C), 129.4 (2C), 129.9 (2C), 130.7, 131.4, 132.7,
133.8, 137.1, 139.0, 141.2, 142.1, 142.6, 146.0, 192.5; HRMS (ESIþ)
Calcd for C27H21O [MþH]þ 361.1592, found 361.1590.
114.5 (2C), 122.6 (2C), 126.9, 130.0, 134.7, 145.1, 152.8, 158.4, 158.6;
HRMS (ESIþ) Calcd for C15H15NO2Br [MþH]þ 322.0286, found
322.0286.
4.3.3. (E)-2-(1,2-Diphenylvinyl)-6-methoxybenzaldehyde
(5ca). Purified by silica gel chromatography (eluent: hexane/
EtOAc¼10:1). Red solid (90%); Mp¼127e128 ꢀC; Rf 0.13 (hexane/
4.2.6. (E)-4-Methoxy-N-(3-(trifluoromethyl)benzylidene)aniline
(1j). Purified by silica gel chromatography (eluent: hexane/EtOAc/
NEt3¼20:1:1). Dark brown solid (98%); Mp¼42e43 ꢀC; 1H NMR
EtOAc¼10:1); 1H NMR (400 MHz, CDCl3):
d 3.95 (s, 3H), 6.82
(400 MHz, CDCl3):
d
3.84 (s, 3H), 6.94 (app. d, J¼8.7 Hz, 2H), 7.26
(d, J¼7.8 Hz, 1H), 6.96e7.07 (m, 3H), 7.08e7.14 (m, 4H), 7.22e7.29
(app. d, J¼8.7 Hz, 2H), 7.58 (t, J¼8.2 Hz, 1H), 7.70 (d, J¼7.8 Hz, 1H),
(m, 5H), 7.49 (t, J¼8.2 Hz, 1H), 10.3 (s, 1H); 13C NMR (100 MHz,
8.05 (d, J¼7.8 Hz, 1H), 8.17 (s, 1H), 8.52 (s, 1H); 13C NMR (100 MHz,
CDCl3): d 56.1, 111.3, 124.0, 124.3, 126.9 (2C), 127.2, 127.7, 128.3
1
CDCl3):
d
55.7, 114.7 (2C), 122.6 (2C), 124.2 (q, JCeF¼274.0 Hz),
(2C), 128.5 (2C), 128.9, 129.5 (2C), 135.4, 137.1, 140.6, 142.5, 144.5,
162.0, 190.5; HRMS (ESIþ) Calcd for C22H19O2 [MþH]þ 315.1385,
found 315.1389.
3
3
125.3 (q, JCeF¼3.8 Hz), 127.5 (q, JCeF¼3.8 Hz), 129.4, 131.5
2
(q, JCeF¼32.6 Hz), 131.9, 137.4, 144.3, 156.4, 158.9; HRMS (ESIþ)
Calcd for C15H13NOF3 [MþH]þ 280.0949, found 280.0952.
4.3.4. (E)-2-(1,2-Diphenylvinyl)-6-(trifluoromethyl)benzaldehyde
(5da). Purified by silica gel chromatography (eluent: hexane/
EtOAc¼25:1) Red solid (68%); Mp¼78e79 ꢀC; Rf 0.12 (hexane/
4.2.7. (E)-N-(2,5-Difluorobenzylidene)-4-methoxyaniline
(1l). Purified by recrystallization from hexane. Yellow solid (70%);
Mp¼66e67 ꢀC; 1H NMR (400 MHz, CDCl3):
d
3.84 (s, 3H), 6.94 (app.
EtOAc¼25:1); 1H NMR (400 MHz, CDCl3):
d 6.88e6.90 (m, 2H),
7.11e7.15 (m, 4H), 7.23e7.34 (m, 4H), 7.46 (d, J¼7.8 Hz, 1H), 7.61
d, J¼9.2 Hz, 2H), 7.08e7.12 (m, 2H), 7.27 (app. d, J¼8.7 Hz, 2H),
7.85e7.89 (m, 1H), 8.74 (d, J¼2.3 Hz, 1H); 13C NMR (100 MHz,
(t, J¼7.8 Hz, 1H), 7.79 (d, J¼7.8 Hz, 1H), 10.7 (q, J¼2.3 Hz, 1H); 13C
CDCl3):
d
55.7, 113.6 (dd, 2JCeF¼24.9 Hz), 114.6 (2C), 117.2 (dd, 2JCeF
,
NMR (100 MHz, CDCl3):
d
126.2 (q, 3JCeF¼5.8 Hz), 127.2 (2C), 127.7,
2
3JCeF¼24.9, 8.6 Hz), 119.2 (dd, 2JCeF
,
3JCeF¼24.9, 8.6 Hz), 122.7 (2C),
128.2, 128.5 (2C), 128.8 (2C), 129.5 (2C), 130.3 (q, JCeF¼32.5 Hz),
125.6e125.8 (m, 1C), 114.3, 149.9, 158.8 (q, 1JCeF¼248.1 Hz), 159.07,
130.5, 132.5, 134.9, 136.1, 136.4, 139.2, 142.0, 143.6, 190.7. The signal
Please cite this article in press as: Yamakawa, T.; Yoshikai, N., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.02.092

T. Yamakawa, N. Yoshikai / Tetrahedron xxx (2013) 1e7
5
of CF3 carbon could not be identified because of signal overlapping
of other peaks; HRMS (ESIþ) Calcd for C22H16OF3 [MþH]þ 353.1153,
found 353.1151.
could not be identified because of signal overlapping with other
peaks; HRMS (ESIþ) Calcd for C22H16OF3 [MþH]þ 353.1153,
found 353.1160.
4.3.5. (E)-2-(1,2-Diphenylvinyl)-6-morpholinobenzaldehyde
(5ea). Purified by silica gel chromatography (eluent: hexane/
EtOAc¼25:1). Red oil (66%); Rf 0.17 (hexane/EtOAc¼10:1); 1H NMR
4.3.11. (E)-4-Methoxy-N-(2-methyl-6-((E)-oct-4-en-4-yl)benzyli-
dene)aniline (3ab). Purified by silica gel chromatography (eluent:
hexane/EtOAc/NEt3¼100:0.5:2.5). Yellow oil (94%); Rf 0.40 (hexane/
(400 MHz, CDCl3):
d
3.02e3.14 (m, 4H), 3.84e3.91 (m, 4H),
EtOAc¼10:1); 1H NMR (400 MHz, CDCl3):
d
0.86 (t, J¼7.3 Hz, 3H),
6.91e6.93 (m, 3H), 7.07e7.17 (m, 5H), 7.23e7.35 (m, 5H), 7.50
0.89 (t, J¼7.3 Hz, 3H), 1.28e1.34 (m, 2H), 1.37e1.43 (m, 2H), 2.16
(q, J¼7.3 Hz, 2H), 2.33e2.37 (m, 2H), 2.66 (s, 3H), 6.92 (app. d,
J¼9.2 Hz, 2H), 7.04 (d, J¼7.3 Hz, 1H), 7.13e7.16 (m, 3H), 7.20e7.25
(t, J¼7.8 Hz, 1H), 10.2 (s, 1H); 13C NMR (100 MHz, CDCl3):
d 53.9,
67.2, 118.2, 125.7, 127.0 (2C). 127.2, 127.5, 127.8, 128.3 (2C), 128.6
(2C), 129.5 (2C), 129.7, 134.8, 137.0, 140.5, 142.7, 145.9, 154.9, 190.7;
(m, 1H), 8.64 (s, 1H); 13C NMR (100 MHz, CDCl3):
d 14.1, 14.4, 21.6,
HRMS (ESIþ) Calcd for
C
25H24NO2 [MþH]þ 370.1807, found
22.1, 23.2, 30.6, 35.0, 55.7, 114.5 (2C), 122.1 (2C), 127.0, 129.0, 130.1,
132.9, 133.0, 138.2, 139.9, 146.0, 147.0, 158.2, 160.7; HRMS (ESIþ)
Calcd for C23H30NO [MþH]þ 336.2327, found 336.2326.
370.1805.
4.3.6. (E)-2-(1,2-Diphenylvinyl)-3,6-dimethoxybenzaldehyde
(5fa). Purified by silica gel chromatography (eluent: hexane/
EtOAc¼15:85). Red solid (76%); Mp¼118e119; Rf 0.10 (hexane/
4.3.12. (E)-4-Methoxy-N-(2-methyl-6-((E)-4-methylpent-2-en-2-yl)
benzylidene)aniline (3ac). Purified by silica gel chromatography
(eluent: hexane/NEt3¼100:2.5). Yellow oil (97%); Rf 0.43 (hexane/
EtOAc¼10:1); 1H NMR (400 MHz, CDCl3):
d 3.55 (s, 3H), 3.89 (s, 3H),
6.96e7.01 (m, 3H), 7.08e7.15 (m, 4H), 7.19 (s, 1H), 7.23e7.35
EtOAc¼10:1); 1H NMR (400 MHz, CDCl3):
d
0.97 (d, J¼6.4 Hz, 6H),
(m, 5H), 10.2 (s, 1H); 13C NMR (100 MHz, CDCl3):
d
56.4, 56.9, 112.2,
1.96 (d, J¼1.4 Hz, 3H), 2.62e2.668 (m, 4H), 3.82 (s, 3H), 5.19
(dd, J¼9.2 Hz, 1.4 Hz, 1H), 6.91e6.94 (m, 4H), 7.06e7.19 (m, 4H),
118.4, 124.3, 126.5 (2C), 127.2, 127.6, 128.3 (2C), 128.5 (2C), 128.8
(2C), 130.3, 133.1, 137.3, 142.0, 151.3, 155.5, 1991.1; HRMS (ESIþ)
Calcd for C23H21O3 [MþH]þ 345.1491, found 345.1488.
7.22e7.25 (m, 1H), 8.61 (s, 1H); 13C NMR (100 MHz, CDCl3):
d 19.1,
22.0, 23.1 (2C), 28.0, 55.7, 114.5 (2C), 122.1 (2C), 126.4, 129.2, 130.0,
132.6, 1332.7, 138.3, 140.4, 145.9, 147.9, 158.2, 160.4; HRMS (ESIþ)
Calcd for C21H26NO [MþH]þ 308.2014, found 308.2016.
4.3.7. (E)-3-Bromo-2-(1,2-diphenylvinyl)-6-methoxybenzaldehyde
(5ga). Purified by silica gel chromatography (eluent: hexane/
EtOAc¼10:1). Yellow solid (59%) Mp¼138e139 ꢀC; Rf 0.07 (hexane/
4.3.13. (E)-N-(3,6-Difluoro-2-((E)-1-phenylprop-1-en-2-yl)benzyli-
dene)-4-methoxyaniline (3ld). Purified by silica gel chromatogra-
phy (eluent: hexane/EtOAc¼25:1). Red oil (92%) consisting of 96:4
mixture of regioisomers as determined by 1H NMR analysis; Rf 0.22
EtOAc¼10:1); 1H NMR (400 MHz, CDCl3):
d 3.92 (s, 3H), 6.93e6.97
(m, 3H), 7.12e7.15 (m, 3H), 7.21 (s, 1H), 7.25e7.32 (m, 5H), 7.78
(d, J¼9.2 Hz, 2H), 10.1 (s, 1H); 13C NMR (100 MHz, CDCl3):
d 56.3,
113.2, 116.6, 125.7, 126.7 (2C), 127.6, 127.9, 128.5 (2C), 128.7 (2C),
128.9 (2C),130.6,136.6,137.7,139.0,140.5,144.0,160.5,190.2; HRMS
(ESIþ) Calcd for C22H18O2Br [MþH]þ 393.0490, found 393.0487.
(hexane/EtOAc¼10:1); 1H NMR (400 MHz, CDCl3):
d 2.23
(d, J¼0.9 Hz, 3H), 3.80 (s, 3H), 6.44 (d, J¼0.9 Hz, 1H), 6.89 (app. d,
J¼9.2 Hz, 2H), 7.05e7.12 (m, 2H), 7.18 (app. d, J¼9.2 Hz, 2H),
7.24e7.39 (m, 6H), 8.59 (s, 1H); 13C NMR (100 MHz, CDCl3):
d 20.0,
4.3.8. (E)-6-(1,2-Diphenylvinyl)-2,3,4-trimethoxybenzaldehyde
(5ha). Purified by silica gel chromatography (eluent: hexane/
EtOAc¼9:1). Red oil (78%); Rf 0.10 (hexane/EtOAc¼10:1); 1H NMR
55.7, 114.6 (2C), 115.8 (dd, J¼25.9 Hz, 9.6 Hz), 118.1 (dd, J¼25.9 Hz,
9.6 Hz), 122.4 (2C), 124.0 (dd, J¼10.5 Hz, 3.8 Hz), 127.2, 128.5 (2C),
129.2 (2C), 131.1,132.6,134.9 (d, J¼19.2 Hz),137.2, 145.2,152.8,155.9
(dd, J¼240.4 Hz), 157.8 (dd, J¼258.7 Hz, 8.6 Hz), 158.8; HRMS (ESIþ)
Calcd for C23H18NOF2 [MþH]þ 362.1356, found 362.1362.
(400 MHz, CDCl3):
d 3.76 (s, 3H), 3.95 (s, 3H), 3.97 (s, 3H), 6.50
(s, 1H), 6.93e6.96 (m, 2H), 7.09e7.13 (m, 4H), 7.26e7.34 (m, 5H),
10.1 (s, 1H); 13C NMR (100 MHz, CDCl3):
d
56.4, 61.4, 62.6, 110.6,
122.5, 126.8 (2C), 127.3, 127.9, 128.4 (2C), 128.6 (2C), 129.2, 129.4
(2C), 136.9, 140.1, 140.2, 142.0, 142.2, 157.0, 158.4, 189.3; HRMS
(ESIþ) Calcd for C24H23O4 [MþH]þ 375.1596, found 375.1599.
4.3.14. (E)-1-Methyl-2-(1-(trimethylsilyl)prop-1-en-2-yl)-1H-indole-
3-carbaldehyde (5ke). Purified by silica gel chromatography (elu-
ent: hexane/EtOAc¼10:1). White solid (86%) consisting of ca. 86:14
mixture of E/Z isomers as determined by 1H NMR analysis;
Mp¼89e91 ꢀC; Rf 0.20 (hexane/EtOAc¼10:1); 1H NMR (400 MHz,
4.3.9. (E)-2-(1,2-Diphenylvinyl)-1-naphthaldehyde (5ia). Purified
by silica gel chromatography (eluent: hexane/EtOAc¼50:1). Red
solid (94%) Mp¼130e131 ꢀC; Rf 0.32 (hexane/EtOAc¼10:1); 1H NMR
CDCl3):
d
0.31 (s, 9H), 2.25 (d, J¼0.9 Hz, 3H), 3.70 (s, 3H), 5.94
(d, J¼0.9 Hz, 1H), 7.29e7.36 (m, 3H), 8.37e8.39 (m, 1H), 9.93 (s, 1H);
(400 MHz, CDCl3):
d
6.92e6.94 (m, 2H), 7.03e7.07 (m, 3H),
13C NMR (100 MHz, CDCl3):
d
ꢂ0.2 (3C), 23.3, 30.7, 109.7, 113.7,
7.27e7.39 (m, 7H), 7.56e7.61 (m, 1H), 7.67 (t, J¼8.2 Hz, 1H), 7.91
122.2, 123.2, 123.9, 125.3, 137.0, 140.8, 140.9, 156.9, 186.0; HRMS
(d, J¼8.2 Hz), 8.08 (d, J¼8.7 Hz, 1H), 9.25 (d, J¼8.7 Hz), 10.5 (s, 1H);
(ESIþ) Calcd for C16H22NOSi [MþH]þ 272.1471, found 272.1467.
13C NMR (100 MHz, CDCl3):
d 126.3, 127.1 (2C), 127.2, 127.7, 128.2,
128.6 (3C), 128.9 (2C), 129.0, 129.1, 129.4, 129.6 (2C), 131.1, 131.5,
4.4. Transformation of ortho-alkenylated aromatic
133.6, 135.6, 136.3, 138.7, 142.7, 147.2, 194.5; HRMS (ESIþ) Calcd for
aldehyde 5ia
C
25H19O [MþH]þ 335.1436, found 335.1432.
4.4.1. 2,3-Diphenyl-1H-cyclopenta[a]naphthalen-1-ol (6). To solu-
tion of 5ia (16.7 mg, 0.05 mol) in CH2Cl2 was added BF3$OEt2
4.3.10. (E)-2-(1,2-Diphenylvinyl)-5-(trifluoromethyl)benzaldehyde
(5ja). Purified by silica gel chromatography (eluent: hexane/
EtOAc¼50:1). Orange oil (53%) consisting of ca. 79:21 mixture of
E/Z isomers as determined by 1H NMR analysis; Rf 0.24 (hexane/
(12.7 m
L, 0.10 mmol) at 0 ꢀC. After stirring for 10 min, the reaction
mixture was quenched with water. The aqueous layer was extrac-
ted with EtOAc (1 mLꢁ3). The combined organic layer was dried
over Na2SO4 and concentrated under reduced pressure. The crude
product was purified by silica gel chromatography (eluent: hexane/
EtOAc¼10:1) to afford the title compound as a white solid (12.8 mg,
74%); Mp¼206e207 ꢀC; Rf 0.12 (hexane/EtOAc¼10:1); 1H NMR
EtOAc¼10:1); 1H NMR (400 MHz, CDCl3, E-isomer):
d 6.62 (s, 1H),
7.13e7.38 (m, 11H), 7.43 (d, J¼8.2 Hz), 7.75 (dd, J¼8.2 Hz, 2.3 Hz,
1H), 10.3 (s, 1H); 13C NMR (100 MHz, CDCl3, E-isomer):
(q, JCeF¼3.8 Hz), 128.2, 128.4 (3C), 129.0 (2C), 129.7 (2C), 130.1
(2C), 131.8, 135.3, 135.9, 136.0, 137.4, 139.6, 151.0, 190.7; The
signals of the CF3 carbon and the aromatic carbon next to CF3
d 125.2
3
(400 MHz, CDCl3):
(d, J¼8.2 Hz, 1H), 7.40e7.48 (m, 8H), 7.57 (t, J¼7.8 Hz, 1H), 7.82
d
f6.07 (d, J¼9.2 Hz), 7.23e7.31 (m, 4H), 7.35
Please cite this article in press as: Yamakawa, T.; Yoshikai, N., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.02.092

6
T. Yamakawa, N. Yoshikai / Tetrahedron xxx (2013) 1e7
(d, J¼8.2 Hz, 1H), 7.88 (d, J¼8.2 Hz, 1H), 8.40 (d, J¼8.2 Hz, 1H); 13C
(d, J¼7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 80.4, 86.1, 120.0,
NMR (100 MHz, CDCl3):
d
77.5, 119.6, 124.4, 125.5, 127.1, 127.5, 128.1,
126.6, 126.7, 127.2, 127.3 (3C), 127.6, 128.3 (2C), 128.4 (4C), 129.4
(2C), 129.6, 129.9, 132.5, 134.3, 137.4, 141.3, 142.6, 142.9; HRMS
(ESIþ) Calcd for C26H18 [MþH]þ 331.1487, found 331.1487.
128.6 (2C), 129.0, 129.2 (2C), 129.4 (2C), 129.5 (2C), 129.7, 130.0,
132.9, 134.1, 135.1, 139.3, 140.0, 141.6, 144.2; HRMS (ESIþ) Calcd for
C
25H19O [MþH]þ 335.1436, found 335.1437.
4.4.5. 1,2-Diphenylphenanthreneaphthalene (9). A mixture of
6
4.4.2. (E)-(2-(1,2-Diphenylvinyl)naphthalen-1-yl)(phenyl)methanol
(33.1 mg, 0.1 mmol) and PtCl2 (2.9 mg, 0.01 mmol) in toluene
(1.0 mL) was stirred at 90 ꢀC for 24 h. The reaction was cooled to
room temperature and then quenched with water. The aqueous
layer was extracted with EtOAc (1 mLꢁ3), and the combined or-
ganic layer was dried over Na2SO4 and concentrated under reduced
pressure. The crude product was purified by silica gel chromatog-
raphy (eluent: hexane) to afford the title compound as a red solid
(27.0 mg, 82% yield). Mp¼148e149 ꢀC; Rf 0.28 (hexane/
(70). To a solution of bromobenzene (23.6 mg, 0.15 mmol) in THF
(1.0 mL) was added nBuLi (1.6 M in hexane, 94
mL, 0.15 mmol)
at ꢂ78 ꢀC. After stirring for 20 min, aldehyde 5ia (33.4 mg,
0.098 mol) was added. The reaction mixture was stirred for 90 min
and then quenched with water while being allowed to room
temperature. The aqueous layer was extracted with EtOAc
(1 mLꢁ3), and the combined organic layer was dried over Na2SO4
and concentrated under reduced pressure. The crude product was
purified by silica gel chromatography (eluent: hexane/
EtOAc¼10:1) to afford the title compound (37.2 mg, 98%). This
compound existed as a 55:45 mixture of rotamers as judged from
1H NMR analysis. Mp¼83e85 ꢀC; Rf 0.24 (hexane/EtOAc¼10:1); 1H
EtOAc¼10:1); 1H NMR (400 MHz, CDCl3):
d 7.17e7.21 (m, 7H),
7.27e7.32 (m, 3H), 7.57e7.68 (m, 4H), 7.72 (d, J¼8.7 Hz, 1H), 7.85
(d, J¼7.8 Hz, 1H), 8.76 (t, J¼8.7 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d
122.1, 122.8, 125.2, 126.2, 126.66 (2C), 126.71, 127.0, 127.6 (2C),
127.8 (2C), 128.4, 127.5, 129.6, 130.0 (2C), 130.1 (2C), 130.8, 131.5,
131.6, 138.5, 139.3, 139.3, 141.8; HRMS (ESIþ) Calcd for C26H19
[MþH]þ 331.1487, found 331.1487.
NMR (400 MHz, CDCl3):
d 1.46e1.48 (m, 1H, major), 1.94e1.95
(m, 1H, minor), 6.41 (d, J¼4.1 Hz, 1H, minor), 6.53 (d, J¼3.2 Hz, 1H,
major), 7.04e7.95 (m, 21H, major, 20H, minor), 8.02 (d, J¼8.7 Hz,
1H, minor); 13C NMR (100 MHz, CDCl3): peaks of the major and the
4.4.6. (E)-2-(1,2-Diphenylvinyl)-1-((4-methoxyphenyl)ethynyl)naph-
thalene (100). To a solution of 8 (332 mg, 1.0 mmol) and 4-
iodoanisole (470 mg, 2.0 mmol) in NEt3 (16 mL) were added
Pd(PPh3)2Cl2 (14.0 mg, 0.02 mmol) and CuI (2.2 mg, 0.01 mmol).
The resulting mixture was stirred at 55 ꢀC for 3 h, followed by
quenching with water at room temperature. The aqueous layer was
extracted with EtOAc (5 mLꢁ3), and the combined organic layer
was dried over Na2SO4 and concentrated under reduced pressure.
The crude product was purified by silica gel chromatography (el-
uent: hexane/EtOAc¼25:1) to afford the title compound as a white
solid (304 mg, 70% yield). Mp¼65e66 ꢀC; Rf 0.23 (hexane/
minor isomers could not be distinguished.
d 72.6, 73.0, 125.87,
125.93, 125.96, 126.01, 126.4, 126.5, 126.7, 127.4, 127.5, 127.6, 127.8,
128.0, 128.07, 128.15, 128.23, 128.4, 128.62, 128.64, 128.80, 128.84,
129.1, 129.2, 129.5, 129.8, 129.9, 130.0, 131.9, 132.1, 134.6, 134.9,
136.1, 136.78, 137.15, 137.9, 138.5, 141.2, 141.5, 142.2, 143.3, 143.5,
143.6; HRMS (ESIþ) Calcd for C31H25O [MþH]þ 413.1905, found
413.1905.
4.4.3. 1,2,3-Triphenyl-1H-cyclopenta[a]naphthalene (7). To a solu-
tion of 70 (19.3 mg, 0.05 mmol) in CH2Cl2 (0.5 mL) was added
BF3$OEt2 (12.7
m
L, 0.10 mmol) at 0 ꢀC then the reaction mixture was
EtOAc¼10:1); 1H NMR (400 MHz, CDCl3):
d 3.78 (s, 3H), 6.77
warmed to room temperature. After stirring for 15 min, the reaction
mixture was quenched with water. The aqueous layer was extrac-
ted with Et2O (1 mLꢁ3). The combined organic layer was dried over
Na2SO4 and concentrated under reduced pressure. The crude
product was purified by silica gel chromatography (eluent¼hexane/
CH2Cl2¼95:5 to 90:10) to afford the title compound as a white solid
(18.2 mg, 99%), (two steps, 97%); Mp¼86e88 ꢀC; Rf 0.40 (hexane/
(d, J¼8.7 Hz, 2H), 7.02e7.06 (m, 5H), 7.17e7.33 (m, 7H), 7.38
(d, J¼8.3 Hz, 2H), 7.51e7.59 (m, 2H), 7.76 (d, J¼8.7 Hz, 1H), 7.85
(d, J¼7.8 Hz, 1H), 8.45 (d, J¼8.2 Hz); 13C NMR (100 MHz, CDCl3):
d
54.5, 85.5, 98.9, 114.0 (2C), 115.8, 121.5, 126.6, 126.8, 127.0,
127.1, 127.4 (2C), 127.5, 128.2 (2C), 128.39, 128.43 (2C), 128.5, 128.8,
129.6 (2C), 129.8, 132.7, 133.2 (2C), 134.0, 137.5, 141.6, 142.1, 143.1,
159.7; HRMS (ESIþ) Calcd for C33H25O [MþH]þ 437.1905, found
437.1907.
EtOAc¼10:1); 1H NMR (400 MHz, CDCl3):
d 5.41 (s, 1H), 7.06e7.13
(m, 6H), 7.16e7.17 (m, 4H), 7.29 (m, 8H), 7.53 (d, J¼8.7 Hz, 1H), 7.78
(d, J¼7.8 Hz, 1H), 7.84 (t, J¼7.8 Hz, 2H); 13C NMR (100 MHz, CDCl3):
4.4.7. 4-Iodo-3-(4-methoxyphenyl)-1,2-diphenylphenanthrene
(10). To a solution of 100 (14 mg, 0.03 mmol) in CH2Cl2 was added
NIS (21 mg, 0.09 mmol) at room temperature. The reaction mixture
was stirred at 50 ꢀC for 12 h, followed by quenching with water at
room temperature. The aqueous layer was extracted with EtOAc
(1 mLꢁ3), and the combined organic layer was dried over Na2SO4
and concentrated under reduced pressure. The crude product was
purified by silica gel chromatography (eluent: hexane) to afford the
title compound as a white solid (15.2 mg, 90% yield). Mp¼245 ꢀC; Rf
d
58.2, 119.7, 123.6, 124.8, 126.4, 126.7, 126.8, 127.5, 127.9 (2C), 128.3,
128.6 (2C), 128.8 (4C), 129.0 (2C), 129.56 (2C), 129.62, 129.8 (2C),
132.5, 135.6, 139.7, 140.2, 143.2, 143.7, 148.1; HRMS (ESIþ) Calcd for
C
31H22 [MþH]þ 395.1800, found 395.1804.
4.4.4. (E)-2-(1,2-Diphenylvinyl)-1-ethynylnaphthalene (8). To a so-
lution of diisopropylamine (168 mL, 1.2 mmol) was added n-BuLi
(1.6 M in hexane, 750
m
L,1.2 mmol) at ꢂ78 ꢀC. The resulting mixture
was allowed to room temperature, stirred for 15 min, and then
0.40 (hexane/EtOAc¼10/1); 1H NMR (400 MHz, CDCl3):
d 3.75
cooled again to ꢂ78 ꢀC, followed by the addition of trimethylsi-
(s, 3H), 6.73e6.89 (m, 7H), 7.04 (app. d, J¼7.8 Hz, 2H), 7.12e7.25
(m, 5H), 7.35 (d, J¼9.2 Hz,1H), 7.59e7.61 (m, 3H), 7.81e7.84 (m, 1H),
lyldiazomethane (2.0 M in hexane, 600 mL, 1.2 mmol). After stirring
for 45 min, aldehyde 5ia (334 mg, 1.0 mol) was added at the same
temperature. The reaction mixture was stirred for 1 h, warmed to
room temperature, and then stirred for additional 10 h before
quenching with water. The aqueous layer was extracted with Et2O
(30 mLꢁ3), and the combined organic layer was washed with brine,
dried over Na2SO4, and concentrated under reduced pressure. The
crude product was purified by silica gel chromatography (eluent:
hexane/EtOAc¼50:1) to afford the title compound as a white solid
(250 mg, 75%); Mp¼83e85 ꢀC; Rf 0.29 (hexane/EtOAc¼10:1); 1H
9.80e9.82 (m, 1H); 13C NMR (100 MHz, CDCl3):
d 55.0, 97.0, 112.7
(2C), 123.7, 124.8, 125.6, 126.6 (3C), 127.4, 127.56 (3C), 127.63, 128.5,
130.8 (2C), 131.0 (3C), 131.5, 132.0 (2C), 132.7, 133.1, 139.1, 139.8,
140.0, 140.1, 140.5, 148.1, 158.2; HRMS (ESIþ) Calcd for C33H24IO
[MþH]þ 563.0870, found 563.0872.
Acknowledgements
We thank the Singapore National Research Foundation (NRF-RF-
2009-05), Nanyang Technological University, and JST, CREST for
financial support.
NMR (400 MHz, CDCl3):
d 3.30 (s, 1H), 6.99e7.07 (m, 5H), 7.17 (s,
1H), 7.24e7.34 (m, 6H), 7.52e7.60 (m, 2H), 7.82e7.88 (m, 2H), 8.38
Please cite this article in press as: Yamakawa, T.; Yoshikai, N., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.02.092

T. Yamakawa, N. Yoshikai / Tetrahedron xxx (2013) 1e7
7
Ed. 2011, 50, 1338; (g) Umeda, N.; Hirano, K.; Satoh, T.; Shibata, N.; Sato, H.;
Miura, M. J. Org. Chem. 2011, 76, 13.
Supplementary data
9. (a) Kakiuchi, F.; Sato, T.; Tsujimoto, T.; Yamauchi, M.; Chatani, N.; Murai, S.
Chem. Lett. 1998, 1053; (b) Kuninobu, Y.; Kikuchi, K.; Tokunaga, Y.; Nishina, Y.;
Takai, K. Tetrahedron 2008, 64, 5974.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.02.092.
10. For related ortho-alkenylation reactions with alkynes using carbonyl-based
directing groups, see: (a) Kakiuchi, F.; Yamamoto, Y.; Chatani, N.; Murai, S.
Chem. Lett. 1995, 681; (b) Lim, S. G.; Lee, J. H.; Moon, C. W.; Hong, J. B.; Jun, C.-H.
Org. Lett. 2003, 5, 2759; (c) Tsuchikama, K.; Kasagawa, M.; Hashimoto, Y. K.;
Endo, K.; Shibata, T. J. Organomet. Chem. 2008, 693, 3939; (d) Shibata, Y.; Otake,
Y.; Hirano, M.; Tanaka, K. Org. Lett. 2009, 11, 689; (e) Schipper, D. J.; Hutchinson,
M.; Fagnou, K. J. Am. Chem. Soc. 2010, 132, 6910; (f) Hashimoto, Y.; Hirano, K.;
Satoh, T.; Kakiuchi, F.; Miura, M. Org. Lett. 2012, 14, 2058; (g) Zhao, P.; Niu, R.;
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11. (a) Lee, P. S.; Fujita, T.; Yoshikai, N. J. Am. Chem. Soc. 2011, 133, 17283; (b) Gao, K.;
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Please cite this article in press as: Yamakawa, T.; Yoshikai, N., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.02.092